Specific binding of [³H]phencyclidines to membrane preparation

Localization of phencyclidine binding sites on alpha and beta subunits of the nicotinic acetylcholine receptor from Torpedo ocellata electric organ using azido phencyclidine

“…However, it was recognized only recently that these drugs may interact directly with the cholinergic ionophore (Kloog et al, 1979Albuquerque et al, 1980;Oswald and Changeux, 1981a). Electrophysiological as well as binding studies Kloog et al, 1980;Oswald and Changeux, 1981a) suggest that PCP acts as a noncompetitive blocker of AcCho. Thus, the drug appears to fall into the pharmacological category of local anesthetics (Webber and Changeux, 1974;Karlin, 1980) and related drugs (Elliott and Raftery, 1979;Albuquerque et al, 1980) rather than that of the cholinergic agonists and their competitive rarine + 1 pM cw-Bgt (0).…”

“…3, Mar. 1984 and ["H]AZ-PCP (defined as the total minus nonspecific binding sites (AcCho binding sites) Oswald and Changeux, 1981a) and its competitive displacement by aminated local anesthetics and other noncompetitive blockers of AcCho Kloog et al, 1980;Oswald and Changeux, 1981a 1, a and b). Quinacrine and the local anesthetic tetracaine inhibited their binding (Fig.…”

“…It is now recognized that PCP can act as a noncompetitive blocker of the nicotinic response to acetylcholine (AcCho). This finding was based on electrophysiological as well as on binding Kloog et al, 1979Kloog et al, , 1980 data indicating that PCP blocks the cholinergic ionophore. PCP does not inhibit binding of the specific nicotinic neurotoxin a-bungarotoxin (a-Bgt) , and binds to specific binding sites in Torpedo electric organ membrane that are distinct from AcCho binding sites Kloog et al, 1979Kloog et al, , 1980Oswald and Changeux, 1981a).…”

“…This finding was based on electrophysiological as well as on binding Kloog et al, 1979Kloog et al, , 1980 data indicating that PCP blocks the cholinergic ionophore. PCP does not inhibit binding of the specific nicotinic neurotoxin a-bungarotoxin (a-Bgt) , and binds to specific binding sites in Torpedo electric organ membrane that are distinct from AcCho binding sites Kloog et al, 1979Kloog et al, , 1980Oswald and Changeux, 1981a). As with other noncompetitive blockers of AcCho (Oswald and Changeux, 1981a;Kloog et al, 1979;Elliott and Raftery, 1979), the binding of PCP is enhanced by the agonist carbamylcholine Oswald and Changeux, 1981a).…”

Stabilization of the high affinity state of the membrane‐bound acetylcholine receptor from Torpedo marmorata by noncompetitive blockers

“…They include, among others, the aminated local anesthetics proadifen and dimethisoquin [3][4][5][6][7], the frog toxin histrionicotoxin (HTX) and its derivatives [8][9][10][11], the hallucinogenic drug phencyclidine [12][13][14]. These pharmacological agents block the physiological response in the/~M range and their binding to saturable sites on ACh-receptor-rich membrane fragments isolated from Torpedo electric organ has been demonstrated with the radiolabelled derivatives [3H]meproadifen [6], [3H] trimethisoquin [ 15 ], [all] perhydro-HTX [ 11,[16][17][18] and [3H]phencyclidine [12,19,20]. A number of structurally unrelated compounds usually considered as primarily interacting with the lipid phase of the membrane, such as the detergents Triton X-100 or Na-cholate [21,22], fatty acids [21,36], phospholipases (reviews [23,27]), general anesthetics and alcohols [7,24[ also block the response to ACh in a noncompetitive manner.…”